To Örebro University

There is evidence that persistent dysregulation of the immune system caused by SARS-CoV-2 infection may increase susceptibility to other infections. Here, we assessed whether it is associated with subsequent diagnoses of infectious mononucleosis due to Epstein-Barr virus (EBV-IM). Residents of Sweden aged 3-100 years without a prior diagnosis of EBV-IM were followed between January 1, 2020, and November 30, 2022, comprising a total of 9 978 860 participants. Individuals were categorized into those without a COVID-19 diagnosis, those with a positive SARS-CoV-2 polymerase chain reaction (PCR) test only - less severe exposure, and those admitted to hospital with COVID-19 - more severe exposure. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the association between the exposure, modeled as a time-varying covariate, and EBV-IM occurrence. EBV-IM rates per 100 000 person-years and 95% CIs were 4.6 (4.4-4.9) for individuals not diagnosed with COVID-19, 7.8 (6.9-8.9) for those with a positive SARS-CoV-2 test only, and 10.5 (6.2-17.6) for patients admitted to hospital with COVID-19. HR and 95% CI were 1.61 (1.39-1.88) for people with a positive PCR test only and 5.71 (3.33-9.79) for those admitted to hospital with COVID-19 compared with people without a COVID-19 diagnosis, after adjustment for birth year, sex, Swedish healthcare region, region of birth, and Charlson comorbidity index. SARS-CoV-2 infection was associated with a subsequent raised risk of EBV-IM, including among those with less severe acute infection, signaling immune perturbation and the possibility of further delayed sequelae linked with EBV-IM.